AV-101 (4-Cl-KYN) is an investigational oral prodrug that targets the N-methyl-D-aspartate receptor (NMDAR), an ionotropic glutamate receptor in the brain. Abnormal NMDAR function is associated with numerous CNS diseases and disorders. The active metabolite of AV-101, 7-chloro-kynurenic acid (7-Cl-KYNA), is a potent and selective full antagonist of the glycine binding site of the NMDAR that inhibits the function of the NMDAR. Unlike ketamine and many other NMDAR antagonists, 7-Cl-KYNA is not an ion channel blocker. In clinical and nonclinical testing completed to date, AV-101 has demonstrated good oral bioavailability and an excellent pharmacokinetic profile. No binding of AV-101 or 7-Cl-KYNA to off-site targets was identified by an extensive receptor screening study. In all clinical trials to date, AV-101 has been very well-tolerated with no psychological side effects or safety concerns and no treatment-related serious adverse events that are often observed with classic channel-blocking NMDAR antagonists such as ketamine and amantadine.

Based on observations and findings from preclinical studies, Vistagen believes that AV-101 has the potential to become a new oral treatment alternative for multiple CNS disorders. Vistagen is currently preparing for Phase 2A development of AV-101, on its own or with collaborators, as a treatment for one or more neurological disorders involving the NMDAR. Multiple studies have shown AV-101 to be safe and well-tolerated, and a range of preclinical studies indicate potential in multiple indications, including levodopa-induced dyskinesia, neuropathic pain, seizures, MDD, and suicidal ideation.

The FDA has granted Fast Track designation for development of AV-101 as a potential adjunctive treatment for MDD and as a non-opioid treatment for neuropathic pain.